A role for TSPO in mitochondrial Ca2+ homeostasis and redox stress signaling

The 18 kDa translocator protein TSPO localizes on the outer mitochondrial membrane (OMM). Systematically overexpressed at sites of neuroinflammation it is adopted as a biomarker of brain conditions. TSPO inhibits the autophagic removal of mitochondria by limiting PARK2-mediated mitochondrial ubiquitination via a peri-organelle accumulation of reactive oxygen species (ROS). Here we describe that TSPO deregulates mitochondrial Ca2+ signaling leading to a parallel increase in the cytosolic Ca2+ pools that activate the Ca2+-dependent NADPH oxidase (NOX) thereby increasing ROS. The inhibition of mitochondrial Ca2+ uptake by TSPO is a consequence of the phosphorylation of the voltage-dependent anion channel (VDAC1) by the protein kinase A (PKA), which is recruited to the mitochondria, in complex with the Acyl-CoA binding domain containing 3 (ACBD3). Notably, the neurotransmitter glutamate, which contributes neuronal toxicity in age-dependent conditions, triggers this TSPO-dependent mechanism of cell signaling leading to cellular demise. TSPO is therefore proposed as a novel OMM-based pathway to control intracellular Ca2+ dynamics and redox transients in neuronal cytotoxicity

An engineered Tetrahymena tRNA(Gln) for in vivo incorporation of unnatural amino acids into proteins by nonsense suppression

A new tRNA, THG73, has been designed and evaluated as a vehicle for incorporating unnatural amino acids site-specifically into proteins expressed in vivo using the stop codon suppression technique. The construct is a modification of tRNAGln(CUA) from Tetrahymena thermophila, which naturally recognizes the stop codon UAG. Using electrophysiological studies of mutations at several sites of the nicotinic acetylcholine receptor, it is established that THG73 represents a major improvement over previous nonsense suppressors both in terms of efficiency and fidelity of unnatural amino acid incorporation. Compared with a previous tRNA used for in vivo suppression, THG73 is as much as 100-fold less likely to be acylated by endogenous synthetases of the Xenopus oocyte. This effectively eliminates a major concern of the in vivo suppression methodology, the undesirable incorporation of natural amino acids at the suppression site. In addition, THG73 is 4-10-fold more efficient at incorporating unnatural amino acids in the oocyte system. Taken together, these two advances should greatly expand the range of applicability of the in vivo nonsense suppression methodology

Precautionary labelling of foods for allergen content: are we ready for a global framework?

© 2014 Allen et al.; licensee BioMed Central Ltd.Food allergy appears to be on the rise with the current mainstay of treatment centred on allergen avoidance. Mandatory allergen labelling has improved the safety of food for allergic consumers. However an additional form of voluntary labelling (termed precautionary allergen labelling) has evolved on a wide range of packaged goods, in a bid by manufacturers to minimise risk to customers, and the negative impact on business that might result from exposure to trace amounts of food allergen present during cross-contamination during production. This has resulted in near ubiquitous utilisation of a multitude of different precautionary allergen labels with subsequent confusion amongst many consumers as to their significance. The global nature of food production and manufacturing makes harmonisation of allergen labelling regulations across the world a matter of increasing importance. Addressing inconsistencies across countries with regards to labelling legislation, as well as improvement or even banning of precautionary allergy labelling are both likely to be significant steps forward in improved food safety for allergic families. This article outlines the current status of allergen labelling legislation around the world and reviews the value of current existing precautionary allergen labelling for the allergic consumer. We strongly urge for an international framework to be considered to help roadmap a solution to the weaknesses of the current systems, and discuss the role of legislation in facilitating this

Experiences of advance care planning in Parkinson’s disease and atypical Parkinsonian disorders: a mixed methods systematic review

Background and purpose: Advance care planning allows people to plan for their future care needs and can include medical, psychological and social aspects. However, little is known on the use, experience of and attitudes towards advance care planning in patients with parkinsonian disorders, their family carers and healthcare professionals. Methods: A systematic search of online databases was conducted in April 2019 using a narrative synthesis approach with thematic analysis and tabulation to synthesize the findings. Results: In all, 507 articles were identified and 27 were included. There were five overarching themes: (i) what is involved in advance care planning discussions, (ii) when and how advance care planning discussions are initiated, (iii) barriers to advance care planning, (iv) the role of healthcare professionals and (v) the role of the family carer. This evidence was used to highlight eight effective components to support optimal advance care planning in parkinsonian disorders: advance care planning discussions should be individualized in content, timing and approach; patients should be invited to discuss advance care planning early and regularly; palliative care services should be introduced early; a skilled professional should deliver advance care planning; support to family carers should be offered in the advance care planning process; healthcare professionals should be educated on parkinsonian disorders and palliative care; advance care planning should be clearly documented and shared with relevant services; and healthcare professionals should be enabled to conduct effective advance care planning. Conclusions: These components can inform best practice in advance care planning in patients with parkinsonian disorders

Stability Measurements of Rutherford Cables with Various Treatments

To improve the stability of Rutherford type superconducting cables, various methods of treating cables were considered and tested. These treatments include strand coating, partial soldering, "barber-pole" insulation and "porous $9 metal" solder filling. To study the effect of these treatments, several cables were prepared and MQE (minimum quench energy) values were measured. Coating, partial soldering or "barber-pole insulation" improved the relative stability$9 for some cables. The "porous metal" filled cables showed higher MQE. However the results suggest that the porous metal process needs to be improved. The measured data for cables with various treatments are presented. (8 refs)

Addressing Food Insecurity in College: Mapping a Shared Conceptual Framework for Campus Pantries in Michigan

The first known university food pantry started at Michigan State University in 1993. Since then, campus food pantries are more widespread, although little is known about them. The current study examined how college pantries best serve students and foster their success. Twentyâ eight food pantry directors and staff from across sixteen Michigan college campuses engaged in concept mapping, a technique used to examine the interrelationships among concepts understood by stakeholders. Analyses identified six concepts, examined importance of each concept as assigned by participants, and evaluated variation among institutions. Implications for findings and future research directions are discussed.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147046/1/asap12161_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147046/2/asap12161.pd

Atomic data from the IRON Project. I. Electron-impact scattering of Fe17+ using <I>R</I>-matrix theory with intermediate coupling

We present results for electron-impact excitation of F-like Fe calculated using R-matrix theory where an intermediate-coupling frame transformation (ICFT) is used to obtain level-resolved collision strengths. Two such calculations are performed, the first expands the target using 2s2 2p5, 2s 2p6, 2s2 2p4 3l, 2s 2p5 3l, and 2p6 3l configurations while the second calculation includes the 2s2 2p4 4l, 2s 2p5 4l, and 2p6 4l configurations as well. The effect of the additional structure in the latter calculation on the n=3 resonances is explored and compared with previous calculations. We find strong resonant enhancement of the effective collision strengths to the 2s2 2p4 3s levels. A comparison with a Chandra X-ray observation of Capella shows that the n=4 R-matrix calculation leads to good agreement with observation</p

Consumption of a High-Fat Meal Alters Post-Prandial SIRT mRNA Expression in Blood Leukocytes

Introduction. Sirtuins (SIRT) are protein deacetylases, hypothesized to regulate the transcription of various genes involved in the prevention of atherogenesis and diet induced obesity. Previous research from our laboratory has demonstrated that consumption of a single, high-fat meal increases various CVD risk factors for up to 5-h post-prandial. Given the importance of SIRT to metabolic disorders, it is reasonable to speculate that a single, high-fat meal also disrupts SIRT. Methods. The purpose of this study was to determine the effect of a high-fat meal (75% of daily kcals & 80% of daily fat needs), on SIRT mRNA expression in blood leukocytes during a 5-h post-prandial period. Men and women (N=17) were recruited to report to the lab following an overnight fast. Venous blood samples were collected prior to the meal, 1, 3, and 5-h post-meal. White buffy coat aliquot was frozen in RNALater solution. At the end of the study samples were thawed and RNA was isolated using a phenol/chloroform method. RNA was reverse transcribed and mRNA expression for SIRT 1-7 was determined using a Taqman qPCR technique with 18S rRNA as a normalizer, under standard PCR cycling conditions. An additional aliquot of serum was used to measure triglyceride, total cholesterol, and glucose responses were measured using enzymatic assays on an automated chemistry analyzer (ChemWell T; P.C., FL). Data was analyzed using a RM ANOVA with P\u3c0.05. Results. Consistent with previous results, the meal caused an increase in triglycerides, total cholesterol and glucose that reached peaked values at 3-h post-prandial. We also observed significant expression changes in the mRNA of the SIRT 1 (P=0.02) and SIRT 6 (P=0.03) during the 5-h post-prandial period. Both SIRT 1 and SIRT 6 showed the greatest decreased expression at 3-h post-prandial compared to baseline, 51.8% and 46.2% respectfully. Conclusion. To our knowledge, this is the 1st study to report that consumption of a high-fat meal transiently alters SIRT mRNA expression consistent with changes in serum triglyceride and glucose concentration. More research is needed to understand how transient, post-prandial changes in SIRT mRNA expression contribute to increased disease risk